Bennett, M.I. (2011). Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: Systematic review. Palliative Medicine, 25, 553–559.
PHASE OF CARE: Not specified
APPLICATIONS: Palliative care
Six studies examined gabapentin, sodium valproate, or phenytoin, and two studies examined amitriptyline or imipramine. In two randomized, controlled trials, (RCTs) opioid doses were varied according to pain intensity, and in five trials, the opioid doses remained stable. The studies of phenytoin and valproate did not report pain intensities. For gabapentin, two RCTs and two observational studies reported an average benefit of 0.8 points (10-point scale, p = 0.025), but the reports of the percent of patients achieving at least a 30% pain relief were mixed. For amitriptyline, one study reported a benefit of 0.9 points of worst pain (p = 0.035), and one abstract did not report results. For gabapentin, adverse event outcomes were inconsistent; one RCT reported withdrawals caused by the medication, including one death. Respiratory depression was reported in two RCTs. Amitriptyline was associated with increased confusion, dry mouth, and drowsiness. The most common side effects were somnolence and dizziness.
The findings of this analysis suggest that the addition of antiepileptics and antidepressants to opioids for cancer-related neuropathic pain management may result in a small improvement in pain intensity at the risk of more adverse events.
Adjuvant medications in addition to opioids for cancer-related neuropathic pain may be helpful for some patients; however, there is a need for skillful use and follow-up to evaluate the effect of adverse events. In some patients, these adverse events were severe. At the same time, the small changes in pain intensity reported here raise the question of whether these differences are clinically relevant and sufficient to warrant the risk of adverse events. Pain management needs to be highly individualized.